Possible Mechanisms for Blunted GH Secretion to GH Secretagogues in Anxiety and Mood Disorders

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Blunted GH responses to GH secretagogues, such as cloni-dine, desipramine, the insulin tolerance test, and others, were thought to detect down-regulation of postsynaptic alpha-2 receptors following excessive central noradrenaline (NA) activity in major depressive disorder (Coplan et al., 1995; Siever et al., 1982). That GH responses are blunted in response to both clonidine and growth hormone releasing factor (GRF) in Panic Disorder (PD) refuted the view that reduced GH response to clonidine simply reflects a specific alpha-2 abnormality. Uhde, Tancer, and Rubinow (1992) have reviewed the possible site(s) where blunting of GH may occur. These include (1) reduced availability of pituitary GH stores secondary to reduced synthesis or excessive secretion (this option seems unlikely as GH responses to the dopamine agonist, apomorphine, are exaggerated in PD); (2) overall hypersecretion of GH with secondary inhibition of GH secretion to secretory stimuli; (3) an abnormally enhanced negative feedback system, that is, increased pituitary sensitivity to the inhibitory effects of GH or somatomedin-C; (4) subsensitivity of the pituitary to the secretory effect of GRF or reduced GRF; (5) failure of clonidine to reduce the inhibitory effect of somatostatin neurons on the pituitary; and (6) abnormal function of a host of other factors previously enumerated. It should be noted that blunted GH secretion is not only observed in PD and depression but also in Generalized Anxiety Disorder (GAD) and possibly Social Phobia. GH responses to GRF and clonidine in childhood depression also tend to be blunted. However, the abnormality is not observed in Schizophrenia or Obsessive-Compulsive Disorder.

Investigators have argued that reduced GH responses to chemical or physiological stimuli in Anxiety and Mood Disorders may represent a trait marker of vulnerability to Mood and Anxiety Disorders. Coplan, Pine, Papp, and Gorman (1997) have presented evidence in both patients with PD as well as in unpredictably reared nonhuman primates that the GH response to the GH secretagogue, clonidine, varies inversely with the degree of HPA axis activation. More recent work with nonhuman primates has provided even stronger evidence of a negative correlation between CRF and GH secretion (Coplan et al., 2000a). Examining juvenile neurochemical levels of CSF, CRF, 5 hydroxy-indole-acetic acid (serotonon metabolite) (5-HIAA), HVA, SOM, 3-methoxy-4-hydroxy phenylglycol (noradrenaline metabolite) (MHPG), and CSF cortisol revealed that only levels of CSF and CRF were significantly correlated with GH response to clonidine. An inverse relationship involving the CRF and HPA axis and GH may be an enduring, trait-like feature observed in association with both stressful early rearing and Mood and Anxiety Disorders.

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Eliminating Stress and Anxiety From Your Life

Eliminating Stress and Anxiety From Your Life

It seems like you hear it all the time from nearly every one you know I'm SO stressed out!? Pressures abound in this world today. Those pressures cause stress and anxiety, and often we are ill-equipped to deal with those stressors that trigger anxiety and other feelings that can make us sick. Literally, sick.

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